title: Evidence of the transient nature of the Th17 phenotype of CD4+CD161+ T cells in the synovial fluid of patients with juvenile idiopathic arthritis.
abstract: OBJECTIVE
  To investigate the phenotype and function of CD4+ T cells in synovial fluid (SF) from the affected joints of children with oligoarticular-onset juvenile idiopathic arthritis (JIA), and to establish a possible link with disease activity.
  
  
  METHODS
  CD4+ T cells were obtained from the peripheral blood (PB) and SF of 23 children with oligoarticular-onset JIA, as well as from the PB of 15 healthy children. The cells were analyzed for the expression of CXCR3, CCR6, and CD161 and for the production of interferon-γ and interleukin-17A (IL-17A). Spectratyping and clonotype analyses were performed to assess different T cell subsets.
  
  
  RESULTS
  The numbers of CD4+CD161+ cells showing either the Th1 or the Th17/Th1 phenotype were higher in the SF than in the PB of children with JIA. The few Th17 cells from JIA SF underwent a spontaneous shift to the Th1 phenotype in vitro, whereas Th17 cells from the PB of healthy children shifted only in the presence of JIA SF; this effect was neutralized by antibody blockade of IL-12 activity. Spectratyping and clonotype analyses showed a similar skewing of the T cell receptor V(β) repertoire in both CD161+ Th17 cells and CD161+ Th1 cells derived from the SF of the same JIA patient. The frequencies of CD4+CD161+ cells, particularly the Th17/Th1 cells, in the JIA SF positively correlated with the erythrocyte sedimentation rate and levels of C-reactive protein.
  
  
  CONCLUSIONS
  These findings suggest that a shifting of CD4+CD161+ T cells from Th17 to the Th17/Th1 or Th1 phenotype can occur in the SF of children with oligoarticular-onset JIA, and indicate that the accumulation of these cells is correlated with parameters of inflammation. Thus, the results support the hypothesis that these cells may play a role in JIA disease activity.
authors.affiliation: University of Florence and Excellence Centre for Research, Transfer and Higher Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies, Florence, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cosmi
authors.forename: Rolando
authors.initials: R
authors.lastname: Cimaz
authors.forename: Laura
authors.initials: L
authors.lastname: Maggi
authors.forename: Veronica
authors.initials: V
authors.lastname: Santarlasci
authors.forename: Manuela
authors.initials: M
authors.lastname: Capone
authors.forename: Francesco
authors.initials: F
authors.lastname: Borriello
authors.forename: Francesca
authors.initials: F
authors.lastname: Frosali
authors.forename: Valentina
authors.initials: V
authors.lastname: Querci
authors.forename: Gabriele
authors.initials: G
authors.lastname: Simonini
authors.forename: Giusi
authors.initials: G
authors.lastname: Barra
authors.forename: Marie Pierre
authors.initials: MP
authors.lastname: Piccinni
authors.forename: Francesco
authors.initials: F
authors.lastname: Liotta
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Palma
authors.forename: Enrico
authors.initials: E
authors.lastname: Maggi
authors.forename: Sergio
authors.initials: S
authors.lastname: Romagnani
authors.forename: Francesco
authors.initials: F
authors.lastname: Annunziato
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D008297:Male; D013582:Synovial Fluid / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D020381:Interleukin-17